The research proposed is designed to understand the mechanisms of recovery from herpesvirus infections and to determine if it is possible to develop immunization protocols that will enhance recovery from recurrent disease. Animal herpesvirus model and in vitro systems will be used to identify the mechanism of action and relative importance of immunological components that control virus dissemination in cell culture. The components to be investigated will include antibody dependent cell cytotoxicity mediated by different cell types, direct lymphocytotoxicity, antibody and complement mediated lysis, immune interferon and other biological mediators released from antigen stimulated lymphocytes. In an attempt to make the investigation more relevant to the in vivo situation, the interrelationships of several components will be measured and evidence for positive and negative interactions recorded. Several antiherpesvirus vaccination protocols will be investigated both for their ability to suppress herpesvirus recrudescent disease in latently infected animals and for their respective efficacy at stimulating different aspects of the immune response. It could be that those individuals subject to frequent Herpes simplex recrudescence have a subtle defect in some aspect of the immune response and that such problems could be corrected by immunopotentiation regimens. It is our hope that these studies may reveal immunopotentiation protocols that could be adapted for human use.